The aim is to gain insight into the genetic basis of organismal diversity by comparing genes and noncoding regions of individuals, populations, and species differing in known ways and to known extents at the organismal level. Another requirement for such studies is that the times since common ancestry be known and short enough so that the record of key genetic changes has not been obscured by later irrelevant changes. Then the tempo of the evolutionary process can be measured, which permits quantitative testing of ideas about the driving force for this process. Two model systems are proposed that meet these requirements, namely the lysozyme and ribosomal DNA systems. Mammalian lysozymes, which normally function as antibacterial agents in diverse parts of the body, provide two opportunities to study adaptive evolution at its most fundamental level, i.e., the nucleotide level. One is offered by two groups of foregut fermenters (ruminants and leaf-eating monkeys) which convergently recruited this enzyme for functioning at low pH in the stomach fluid. The other, offered by mice, involves a recent duplication of the lysozyme gene, after which one of the two descendant genes became optimized for functioning at pH 8 in the intestinal fluid. Extensive sequencing of cloned and enzymatically amplified regions combined with chromosome mapping and walking and transient expression tests should permit characterization of the lysozyme gene clusters in several species, identification of regulatory sequences, and elucidation of the mechanism of gene amplification and concerted evolution in such clusters. Site-directed mutagenesis, followed by expression of lysozyme genes in yeast and then catalytic and physicochemical studies of the purified lysozymes, will enable testing of ideas about the genetic basis of adaptive evolution in proteins. It is proposed that tandem arrays of rDNA repeats offer a hitherto unsuspected opportunity to link molecular to organismal evolution. The possibility that the rate of rDNA evolution by positive selection and recombination is geared to the rate of morphological change in animals will be examined by directly sequencing 28S rRNA genes and measuring the sizes of rDNA repeats for selected pairs of taxa exemplifying fast and slow phenotypic evolution-a project that brings together the morphometric approach developed by this laboratory for quantitating knowledge of organismal diversity and a molecular approach aimed at finding out what types of mutations account for organismal differences.